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FOXO1 在脂肪细胞分化中的分子机制。

Molecular mechanisms of FOXO1 in adipocyte differentiation.

机构信息

Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.

Nanchang Joint Programme, Queen Mary, University of London, London, UK.

出版信息

J Mol Endocrinol. 2019 Apr 1;62(3):R239-R253. doi: 10.1530/JME-18-0178.

Abstract

Forkhead box-O1 (FOXO1) is a downstream target of AKT and plays crucial roles in cell cycle control, apoptosis, metabolism and adipocyte differentiation. It is thought that FOXO1 affects adipocyte differentiation by regulating lipogenesis and cell cycle. With the deepening in the understanding of this field, it is currently believed that FOXO1 translocation between nuclei and cytoplasm is involved in the regulation of FOXO1 activity, thus affecting adipocyte differentiation. Translocation of FOXO1 depends on its post-translational modifications and interactions with 14-3-3. Based on these modifications and interactions, FOXO1 could regulate lipogenesis through PPARγ and the adipocyte cell cycle through p21 and p27. In this review, we aim to provide a comprehensive FOXO1 regulation network in adipocyte differentiation by linking together distinct functions mentioned above to explain their effects on adipocyte differentiation and to emphasize the regulatory role of FOXO1. In addition, we also focus on the novel findings such as the use of miRNAs in FOXO1 regulation and highlight the improvable issues, such as RNA modifications, for future research in the field.

摘要

叉头框蛋白 O1(FOXO1)是 AKT 的下游靶标,在细胞周期控制、细胞凋亡、代谢和脂肪细胞分化中发挥关键作用。人们认为 FOXO1 通过调节脂肪生成和细胞周期来影响脂肪细胞分化。随着对该领域的深入了解,目前认为 FOXO1 在核和细胞质之间的易位参与了 FOXO1 活性的调节,从而影响脂肪细胞分化。FOXO1 的易位取决于其翻译后的修饰和与 14-3-3 的相互作用。基于这些修饰和相互作用,FOXO1 可以通过 PPARγ 调节脂肪生成,通过 p21 和 p27 调节脂肪细胞周期。在这篇综述中,我们旨在通过将上述不同功能联系起来,为脂肪细胞分化中的 FOXO1 调节网络提供一个全面的概述,以解释它们对脂肪细胞分化的影响,并强调 FOXO1 的调节作用。此外,我们还重点介绍了 miRNA 在 FOXO1 调节中的新发现,并强调了 RNA 修饰等可改进的问题,为该领域的未来研究提供参考。

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